Through doping، we understand the use by athletes of substances prohibited by the anti-doping agencies in order to gain a competitive advantage. Since sport plays an important role in physical and mental education and in promoting international understanding and cooperation، the widespread use of doping products and methods has consequences not only on health of the athletes، but also upon the image of sport. Thus، doping in sports is forbidden for both ethical and medical reasons. Narcotics and analgesics، anabolic steroids، hormones، selective androgen receptor modulators are among the most frequently utilized substances. Although antidoping controls are becoming more rigorous، doping and، very importantly، masking doping methods are also advancing، and these are usually one step ahead of doping detection techniques. Depending on the sport practiced and the physical attributes it requires، the athletes will look for one or more of the following benefits of doping: recovering from an injury، increasing body recovery capacity after training، increasing muscle mass and strength، decreasing fat tissue، increasing endurance. Finally، when we look once again at a doping scandal، amazed at how much animosity against those caught can exist; the question is: is it really such a disaster as presented by the media or a silent truth under our eyes، but which many of us have refused to accept?

Since two decades or so transdermal route established itself as better alternative to traditional oral route. This is possible due to continuous innovations in transdermal drug delivery (TDD)، which not only enables researchers from academia and industry to successfully develop and launch many new pharmaceuticals but also allow to include new classes of drugs that can be developed into transdermal formulations. These successes are achieved due to the use of novel techniques based on either physical or chemical approaches. However، both of these techniques suffer due to their own disadvantages. Comparatively، a simple method of supersaturation to enhance drug permeation across skin has created a new wave of interest. Even though the application supersaturated principle in topical and TDD has been used from 1960s، but proper control of drug release and formation of stable supersaturated states has been the core of intense research in the last decade. Out of various methods used to get supersaturated system، evaporation method is considered as most efficient and practically feasible for TDD. Therefore، in this review concept of supersaturation، selection of solvent system and the mechanism of inhibition of crystallization are discussed. Application of evaporation systems in the development of transdermal formulations such as solutions، semisolids and metered dose therapeutic systems (MDTS) and the commercial evaporative systems are also discussed in this review.

Peptide nucleic acids (PNA) are synthetic analog of DNA with a repeating N-(2-aminoethyl)-glycine peptide backbone connected to purine and pyrimidine nucleobases via a linker. Considering the unique properties of PNA، including resistance to enzymatic digestion، higher biostability combined with great hybridization affinity toward DNA and RNA، it has attracted great attention toward PNA- based technology as a promising approach for gene alteration. However، an important challenge in utilizing PNA is poor intracellular uptake. Therefore، some strategies have been developed to enhance the delivery of PNA in order to reach cognate site. Although PNAs primarily demonstrated to act as an antisense and antigene agents for inhibition of transcription and translation of target genes، more therapeutic applications such as splicing modulation and gene editing are also used to produce specific genome modifications. Hence، several approaches based on PNAs technology have been designed for these purposes. This review briefly presents the properties and characteristics of PNA as well as different gene modulation mechanisms. Thereafter، current status of successful therapeutic applications of PNA as gene therapeutic intervention in different research areas with special interest in medical application in particular، anti-cancer therapy are discussed. Then it focuses on possible use of PNA as anti-mir agent and PNA-based strategies against clinically important bacteria.

Diabetes Mellitus (T2DM) as a chronic disease، is on rise in parallel with other non-communicable diseases. Several studies have shown that probiotics and prebiotics might exert beneficial effects in chronic diseases including diabetes. Because of controversial results from different trials، the present study aims to assess the effects of prebiotic/synbiotic consumption on metabolic parameters in patients with type2 diabetes.

Methods

A systematic literature search was performed on randomized controlled trial published in PubMed/Medline، SciVerse Scopus، Google scholar، SID and Magiran up to March 2018. Of a total number of 255 studies found in initial literature search، ten randomized controlled trials were included in the meta-analysis. The pooled mean net change were calculated in fasting blood-glucose [FBG]، Hemoglobin A1c [HbA1c] and lipid markers (total cholesterol [TC]، triglyceride [TG]، low-density lipoprotein cholesterol [LDL-C]، high density lipoprotein cholesterol [HDL-C]). The meta-analyses was conducted using Revman Software (v5.3).

Results

The pooled estimate indicated a significant difference for the mean change in FBG، HbA1c and HDL in treatment group in comparison with control group. Subgroup analysis by intervention showed a significant difference in TG، LDL and HDL (synbiotic group) and in TG، TC، FBG، HDL and HbA1c (prebiotic group) compared with placebo. In another subgroup analysis، high quality studies showed significant reductions in TG، TC، FBG and HbA1c in intervention group compared with placebo group.

Conclusion

In summary، diets supplemented with either prebiotics or synbiotics can result in improvements in lipid metabolism and glucose homeostasis in type 2 diabetic patients.

Multiple sclerosis is a complex autoimmune disorder which characterized by demyelination and axonal loss in the central nervous system (CNS). Several evidences indicate that some new drugs and stem cell therapy have opened a new horizon for multiple sclerosis treatment، but current therapies are partially effective or not safe in the long term. Recently، herbal therapies represent a promising therapeutic approach for multiple sclerosis disease. Here، we consider the potential benefits of some herbal compounds on different aspects of multiple sclerosis disease. The medicinal plants and their derivatives; Ginkgo biloba، Zingiber officinale، Curcuma longa، Hypericum perforatum، Valeriana officinalis، Vaccinium macrocarpon، Nigella sativa،Piper methysticum، Crocus sativus، Panax ginseng، Boswellia papyrifera، Vitis vinifera، Gastrodia elata، Camellia sinensis، Oenothera biennis، MS14 and Cannabis sativa have been informed to have several therapeutic effects in MS patients.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein nuclease (Cas) is identified as an adaptive immune system in archaea and bacteria. Type II of this system، CRISPR-Cas9، is the most versatile form that has enabled facile and efficient targeted genome editing. Viral infections have serious impacts on global health and conventional antiviral therapies have not yielded a successful solution hitherto. The CRISPR-Cas9 system represents a promising tool for eliminating viral infections. In this review، we highlight 1) the recent progress of CRISPR-Cas technology in decoding and diagnosis of viral outbreaks، 2) its applications to eliminate viral infections in both pre-integration and provirus stages، and 3) various delivery systems that are employed to introduce the platform into target cells.

Molecular imaging is one of the import methods for recognition of cancer at the early stage in order to enhance the capacity of remedy. This study was aimed to introduce a new contrast agent that was targeted with CD24 so as to improve the CT scan detection of cancer cells with higher CD24 expression.

Methods

The surface modifications of gold nanoparticles (Au-NPs) were done with long PEG (HS-PEG-CH3O) and short PEG (HS-PEG-COOH) chains to enhance their stability and capacity for immobilization of different antibodies. MTT assay was carried out to assess the biocompatibility of the NPs. The obtained contrast agent was implemented in the targeted CT imaging based on in vitro and in vivo studies of breast cancer.

Results

The results revealed that the attached CD24 to the cell surface of PEGylated Au-NPs could enhance significantly the cells CT number (40.45 HU in 4T1، while it was 16.61 HU in CT26) It was shown that the attenuation coef?cient of the molecularly targeted cells was more than 2 times excessive than the control groups. Further، the tumor region in model of xenograft tumor has higher density compare to the omnipaque groups، 60 min after injection (45 Hu vs.81 Hu). These results showed that the nanoparticles stayed in tumor region for longer time.

Conclusion

It is predicted that the synthesized nanoparticle can be used as computed tomography contrast agent. Also، it can be used to identify the tumor cells with higher expression of CD24 at the early stages more efficiently compare to the other routine methods.

To potentially enhance the bioavailability and extend the bioactivity effectiveness of Isoleucine-Proline-Proline (IPP، an antihypertensive bioactive peptide of dairy origin)، a novel Lyotropic Liquid Crystalline Pharmacosomal Nanoparticle (LLCPNP) was synthesized، and its physicochemical and technological characteristics were studied.

Methods

LLCPNPs precursors were developed using IPP and soy phosphatidylcholine via complex formation. Polarized light microscopy، small angle X-ray scattering، differential scanning calorimetry، dynamic light scattering and Fourier transform infrared spectroscopy were employed to characterize the physicochemical properties of the nanoparticles. The in-vitro release and its related mechanisms were also studied.

The present study results emphasized that LLCPNPs could be proposed as an unrivaled carrier to promote the bioavailability، stability and shelf-life of nutraceutical and biopharmaceutical formulations containing bioactive peptides.

Biopharmaceutics classification system (BCS) class IV compounds، exhibits least oral bioavailability، low solubility and intestinal permeability among all pharmaceutical classes of drugs. Thus، these drugs need more compatible and efficient delivery system. Since، their solubility in various medium، remains a limitation so، polymeric nano coacervates based drug loading with modified approach for them may prove to be a solution ahead. Therefore، in present study Chitosan is opted for encapsulating the BCS class IV drug (Hydrochlorothiazide) to attain better stability، enhanced permeability and lower toxicity.

Methods

For this study، Hydrochlorothiazide (HCTZ) was opted for formulating chitosan based nano-coacervate system.

Results

Optimized HCTZ nanocoacervates exhibited the average particle size of 91.39 ± 0.75 nm with Poly-dispersity index score of 0.159 ± 0.01، indicating homogeneity of colloidal solution. Zeta potential and encapsulation efficiency of HCTZ nanocoacervates were recorded as -18.9 ± 0.8 mV and 76.69 ± 0.82 % respectively. Further، from TEM and SEM evaluation the average particle size for the same were found in conformity (35-50 nm)، with almost spherical morphology. Also، the EDX (Electron Dispersive X-ray) spectrometry and FT – IR analysis of optimized formulation indicated the balanced chemical composition and interaction between the polymeric molecules. The HCTZ nano coacervates showed the linear diffusion profile through the dialysis membrane.

Conclusion

We can conclude from the present study that the optimized HCTZ nano coacervates may prove to be a suitable potential option for effective delivery of BCS class IV drugs.

Lately، bismuth-based nanomaterials have been widely utilized in medical researches such as imaging، drug delivery and radio-sensitization. Despite their advantages، bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study، we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines.

Methods

Bi2O3 NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10، 20، 50 and 100 μg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also، apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis، respectively.

Results

Bi2O3 NPs were successfully synthesized with average size of 19.2 ± 6.5 nm، then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 μg/ml for both compounds.

Conclusion

Results indicated low cytotoxicity of the prepared NPs at lower incubation periods، which is very important for their further applications. However، 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.

Electrochemical measurements have prompted the progress as a consequence of their affectability، cost-affectivity and comparatively short examination time. The aim of this study was the fast evaluation of the effect of chemotherapy compounds on the viability of lung cancer cells (A549) via electrochemical methods.

Methods

Cyclic voltammetry (CV) was used as a primary method to distinguish between electrochemical behavior of normal and lung cancer cells. Differential pulse voltammetry (DPV) was employed as a complementary analyses method for the impact of doxorubicin (DOX) and Flavonoid modified drug (FMD) (US patent Application number: 62548886) on Lung cancer cells.

Results

Only one oxidative peak، at approximately -0.15 V was detected through DPV method in cancer cell line. While a significant distinguish was not seen in CV. The current intensity (I) was decreased in cancer cells with increasing the DOX and FMD levels (t=99.027، α=0.05، P=0.0000)، (t=135.513، α=0.05، P=0.0000)، respectively.

Conclusion

The movement of cancerous cells towards death through chemotherapy drugs such as DOX and FMD can make distinct and significant changes in the electrochemical behaviors of those cells.

Cartilage shows neither repairs nor regenerative properties after trauma or gradual wear and causes severe pain due to bones rubbing. Bioprinting of tissue-engineered artificial cartilage is one of the most fast-growing sciences in this area that can help millions of people against this disease.

Methods

Bioprinting of proper bioscaffolds for cartilage repair was the main goal of this study. The bioprinting process was achieved by a novel composition consisting of alginate (AL)، Halloysite nanotube (HNT)، and methylcellulose (MC) prepared in bio-ink. Also، the effect of Russian olive (RO) in chondrocytes growth on bioscaffolds was also investigated in this work. Compressive، hardness and viscosity tests، Energy-Dispersive X-Ray Spectroscopy (EDX)، Fourier-Transform Infrared Spectroscopy (FT-IR)، Differential Scanning Calorimetry (DSC)، water-soluble Tetrazolium (WST) assay، and also transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were carried out.

Results

The results show that in constant concentrations of AL، MC، and RO (20 mg/ml AL، 20 mg/ml MC، and 10 mg/ml RO) when concentration of HNT increased from 10 mg/ml (T-7) to 20 mg/ml (T-8) compressive stiffness increased from 241±45 kPa to 500.66±19.50 kPa. Also، 20 mg/ml of AL in composition saved proper water content for chondrocyte growth and produced good viscosity properties for a higher printing resolution.

Conclusion

RO increased chondrocytes living cell efficiency by 11% on bioprinted scaffolds in comparison with the control group without RO. Results obtained through in-vivo studies were similar to those of in-vitro studies. According to the results، T-7 bio-ink has good potential in bioprinting of scaffolds in cartilage repairs.

Assessment of drug substance and excipients compatibility is an important issue during pre-formulation studies as well as the quality control of pharmaceutical dosage forms. In this study، potential incompatibility between methyldopa and reducing excipients was evaluated using physicochemical methods.

Methods

Dextrose and lactose (anhydrous & monohydrate) were selected as reducing carbohydrates. The initial incompatibility was studied with DSC and FTIR on binary mixtures with 1:1 mass ratio. Results were confirmed using HPLC studies coupled with mass spectrometry.

Results

The DSC curves indicated the elimination of the melting endotherm of methyldopa in the binary mixtures. A new peak at 1719 cm-1 was observed in the FTIR spectra that can be attributed to the loss of type one amine functionality. The m/z of the proposed compound was observed in the mass spectra.

Conclusion

The potential incompatibility of Methyldopa with reducing carbohydrates was established using physicochemical methods.

Pancreatic adenocarcinoma has a high prevalence all over the world. Most of the therapeutic approaches failed as a result of tumor invasion and rapid metastasis. Several natural plants have been shown to have promising therapeutic effects. Thus، the aim of this study was to investigate the cytotoxic activity of Eryngium billardieri against PANC-1 cancer cell lines.

The results of the MTT assay showed that E. billardieri extracts had cytotoxic effects on PANC- 1 cancer cell lines. Moreover، the ?ndings from the gene expression confirmed the over expression of Bax، and under expression of cyclin D1 following treatment with dichloromethane (DCM) and n-hexane (n- hex) extracts in cancer cells (P < 0.05). Interestingly، the ?ow cytometry results showed that DCM and n- hex extracts of E. billardieri induced apoptosis in PANC- 1 cancer cell lines.

Conclusion

The results of this study demonstrated that DCM and n- hex extracts of E. billardieri significantly induce apoptosis by increasing Bax and decreasing cyclin D1 mRNA expression. Therefore، E. billardieri may be regarded as a novel approach for treatment of pancreatic cancer as a result of its promising apoptotic and cytotoxic properties.

Streptomyces sp.، a dominant genus in Actinomycetes، is the source of a wide variety of secondary metabolites. Microbial metabolites can be utilized as novel anticancer agents; with fewer side effects. The present article illustrated the anti-carcinogenic effect of the ether extracted organic metabolites derived from Streptomyces bacteria on SW480 colon cancer cell line.

Methods

MTT assay was performed in order to investigate the cytotoxicity effect of metabolites on SW480 cells. Apoptosis and cell cycle arrests were measured by flowcytometry. Morphological changes were indicated by Propidium iodide staining andP53 gene expression was evaluated by real-time PCR.

The increased demand for probiotics because of their health purposes provides the context for this study، which involves the molecular identification of lactic acid bacteria (LAB) obtained from the vaginal microbiota of healthy fertile women. The isolates were subjected for examination to prove their probiotic potential. In particular، the isolates were subjected to various tests، including acid/bile tolerance، antimicrobial activity، antibiotic susceptibility، Gram staining، and catalase enzyme activity assessment.

Methods

Several methods were utilized for the molecular identification of the isolates، including ARDRA، (GTG)5-PCR fingerprinting، and the PCR sequencing of 16S-rDNA amplified fragments. Disc diffusion and well diffusion methods were used to assess antibiotic susceptibility and antibacterial activity of isolates. Tolerance to acid and bile was performed at pH 2.5 and 0.3% bile oxgall.

Results

A total of 45 isolates of 88 separate organisms was selected. All of the isolates demonstrated an antibacterial effect on the exploited indicator microorganisms. All selected strains also maintained their viability at low-pH and high-bile salt conditions and exhibited abroad variation in their survival. Only the Enterococcus avium strain showed resistance to all 9 tested antibiotics. Based on the molecular identification and clustering، the 45 isolated bacteria were classified into three major groups of LAB: Enterococcus، Lactobacillus and Lactococcus.

Conclusion

LAB are microorganisms that have a particularly important function in maintaining the health of the vaginal and gastrointestinal tract and in protecting it from infection by other pathogenic organisms. The isolates found to be a promising probiotic candidate by showed desirable characteristics. Therefore، strain DL3 can be used as natural food preservative with some more potential investigations.

Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study، we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1، IL-13R1، Dual oxidase 1 (DUOX1) and DUOX2. In addition، we examined the potential protective effect of metformin in these cytokines and genes، as well as histopathological changes in rat’s lung tissues.

Methods

20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks، rats were sacrificed and their lung tissues were removed for histopathological، real-time PCR and ELISA assays.

Results

Irradiation of lung was associated with an increase in IL-4 cytokine level، as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However، there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover، histopathological evaluations showed significant infiltration of lymphocytes and macrophages، fibrosis، as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level، associated with amelioration of pathological changes.

Conclusion

Results of this study showed remarkable pathological damages، an increase in the levels of IL-4، IL4Ra1 and Duox2، while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4–DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.

Manganism is a cognitive disorder take places in peoples are exposed to environmental manganese pollution. Overexposure to manganese ion (Mn2+) mainly influences central nervous system and causes symptoms that increase possibility of hippocampal damages.

Methods

In this study rats were administrated by two different doses of MnCl2 and behavioral and physiological consequences were evaluated. We also investigated effects of E. Amoenum on Mn2+-imposed toxicity by behavioral، biochemical، immunoblotting and histological studies on hippocampus tissue.

In all types of ischemic stroke، especially in the acute phase، excessive oxidative stress causes structural and functional damage to the brain. This may play a major role in the pathophysiology of the brain damage. Higher serum levels of bilirubin have therapeutic effects in oxidative stress-induced stroke. Nevertheless، role of increased serum levels of bilirubin in the acute phase of ischemic stroke is controversial.

Methods

This study was a cross-sectional prospective descriptive study conducted in the Emergency Department (ED) of Imam Reza hospital، Tabriz University of Medical Sciences، Tabriz، Iran، throughout six months. 275 ischemic stroke patients were evaluated based on their brain CT scan infarct size، NIHSS، MRS، and serum levels of bilirubin. Later، data were analyzed using SPSS software.

To develop fast dissolving oral film to address vomiting and nausea in pediatric population.

Methods

Oral films of Dimenhydrinate were prepared by solvent casting method by using hydroxypropylmethyl cellulose E5 (HPMC E5)، polyethylene glycol 400 (PEG 400) and croscarmellose sodium. Solubility of dimenhydrinate was enhanced by ethanol as a co-solvent. To make dimenhydrinate palatable sodium saccharin and peppermint oil were used. All films were evaluated for mechanical parameters، surface pH، morphology، disintegration time and percent dissolution.

The main and corresponding author، "Mohammad Tasyriq Che Omar" submitted this article to the "Advanced Pharmaceutical Bulletin" Journal on 20 of April 2017 and it was published after positive reviews in: Adv Pharm Bull، 2017، 7(2)، 299-312، doi: 10.15171/apb.2017.036. Recently we were informed by an email that this work was carried out under direct supervision of a researcher in the "Advanced Medical and Dental Institute، Universiti Sains Malaysia" between 2013-2016. On the submitted and published manuscript "Mohammad Tasyriq Che Omar" did not include the name of his supervisor as an author، who substantially contributed to conception and design of the work. No permission was obtained from the supervisor for submission of this work. We contacted "Mohammad Tasyriq Che Omar" regarding this issue and he admitted this mistake. He requested to add his supervisor’s name on the published paper. This could not be happened as it is against the current regulations and professional ethics. Publication of this work without the knowledge، consent، and permission of the PhD supervisor and without his name is unacceptable and reflective of extremely poor professional ethics. The editors of the "Advanced Pharmaceutical Bulletin" Journal who act according to the COPE Code of Conduct، consider this an infringement of professional ethics and the decision has been made to retract the article published in the Journal. The editors of "Advanced Pharmaceutical Bulletin" Journal are sorry for any inconveniences caused to the reviewers، editorial staff and to the readers. Prof Hadi Valizadeh "Advanced Pharmaceutical Bulletin" Editor-in-Chief